Ontology type: schema:ScholarlyArticle Open Access: True
2018-05-15
AUTHORSNeale T. Hanke, Elliot Imler, Marilyn T. Marron, Bruce E. Seligmann, Linda L. Garland, Amanda F. Baker
ABSTRACTPurposeWe previously showed that carfilzomib (CFZ) has potent anti-proliferative and cytotoxic activity in a broad range of lung cancer cell lines. Here we investigate possible mechanisms of CFZ acquired resistance in lung cancer cell lines.MethodsCFZ-resistant non-small cell lung cancer (NSCLC) cell lines were developed by exposing A549 and H520 cells to stepwise increasing concentrations of CFZ. Resistance to CFZ and cross-resistance to bortezomib and other chemotherapy drugs was measured using the MTT assay. Cytotoxicity to CFZ was determined using a CytoTox assay. Western blot was used to measure apoptosis, autophagy, and drug efflux transporter-related proteins. Quantitative targeted whole transcriptome sequencing and quantitative RT-PCR was used to measure gene expression. Flow cytometry was used to analyze intracellular accumulation of doxorubicin.ResultsThe CFZ IC50 value of the resistant cells increased versus parental lines (2.5-fold for A549, 122-fold for H520). Resistant lines showed reduced expression of apoptosis and autophagy markers and reduced death versus parental lines following CFZ treatment. Both resistant lines exhibited higher P-glycoprotein (Pgp) gene (TempO-Seq® analysis, increased 1.2-fold in A549, > 9000-fold in H520) and protein expression levels versus parental lines. TempO-Seq® analysis indicated other drug resistance pathways were upregulated. The resistant cell lines demonstrated less accumulation of intracellular doxorubicin, and were cross-resistant to other Pgp client drugs: bortezomib, doxorubicin, and paclitaxel, but not cisplatin.ConclusionsUpregulation of Pgp appears to be an important, but not the only, mechanism of CFZ resistance in NSCLC cell lines. More... »
PAGES1317-1327
http://scigraph.springernature.com/pub.10.1007/s00432-018-2662-0
DOIhttp://dx.doi.org/10.1007/s00432-018-2662-0
DIMENSIONShttps://app.dimensions.ai/details/publication/pub.1103994980
PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/29766327
JSON-LD is the canonical representation for SciGraph data.
TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT
[
{
"@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json",
"about": [
{
"id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Medical and Health Sciences",
"type": "DefinedTerm"
},
{
"id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1112",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Oncology and Carcinogenesis",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "A549 Cells",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "ATP Binding Cassette Transporter, Subfamily B, Member 1",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Antineoplastic Agents",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Carcinoma, Non-Small-Cell Lung",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Cell Death",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Cell Line, Tumor",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Cell Proliferation",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Drug Resistance, Neoplasm",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Humans",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Lung Neoplasms",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Oligopeptides",
"type": "DefinedTerm"
}
],
"author": [
{
"affiliation": {
"alternateName": "College of Medicine, University of Arizona Cancer Center, Tucson, AZ, USA",
"id": "http://www.grid.ac/institutes/grid.134563.6",
"name": [
"College of Medicine, University of Arizona Cancer Center, Tucson, AZ, USA"
],
"type": "Organization"
},
"familyName": "Hanke",
"givenName": "Neale T.",
"id": "sg:person.01231024471.66",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01231024471.66"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "BioSpyder Technologies Inc, Carlsbad, CA, USA",
"id": "http://www.grid.ac/institutes/grid.465144.6",
"name": [
"BioSpyder Technologies Inc, Carlsbad, CA, USA"
],
"type": "Organization"
},
"familyName": "Imler",
"givenName": "Elliot",
"id": "sg:person.01323346006.87",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01323346006.87"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "BioSpyder Technologies Inc, Carlsbad, CA, USA",
"id": "http://www.grid.ac/institutes/grid.465144.6",
"name": [
"BioSpyder Technologies Inc, Carlsbad, CA, USA"
],
"type": "Organization"
},
"familyName": "Marron",
"givenName": "Marilyn T.",
"id": "sg:person.01343121163.54",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01343121163.54"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "BioSpyder Technologies Inc, Carlsbad, CA, USA",
"id": "http://www.grid.ac/institutes/grid.465144.6",
"name": [
"BioSpyder Technologies Inc, Carlsbad, CA, USA"
],
"type": "Organization"
},
"familyName": "Seligmann",
"givenName": "Bruce E.",
"id": "sg:person.01014063606.33",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01014063606.33"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "College of Medicine, University of Arizona Cancer Center, Tucson, AZ, USA",
"id": "http://www.grid.ac/institutes/grid.134563.6",
"name": [
"College of Medicine, University of Arizona Cancer Center, Tucson, AZ, USA"
],
"type": "Organization"
},
"familyName": "Garland",
"givenName": "Linda L.",
"id": "sg:person.01322145005.35",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01322145005.35"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Ventana Medical Systems, Inc., A Member of the Roche Group, 1910 East Innovation Park Drive, 85755, Tucson, AZ, USA",
"id": "http://www.grid.ac/institutes/grid.418158.1",
"name": [
"College of Medicine, University of Arizona Cancer Center, Tucson, AZ, USA",
"Ventana Medical Systems, Inc., A Member of the Roche Group, 1910 East Innovation Park Drive, 85755, Tucson, AZ, USA"
],
"type": "Organization"
},
"familyName": "Baker",
"givenName": "Amanda F.",
"id": "sg:person.01067534552.92",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01067534552.92"
],
"type": "Person"
}
],
"citation": [
{
"id": "sg:pub.10.1007/978-3-319-06752-0_5",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1040589924",
"https://doi.org/10.1007/978-3-319-06752-0_5"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1007/s00280-013-2267-x",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1034718690",
"https://doi.org/10.1007/s00280-013-2267-x"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1186/1476-4598-9-110",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1010792359",
"https://doi.org/10.1186/1476-4598-9-110"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1007/s00432-015-2047-6",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1052308469",
"https://doi.org/10.1007/s00432-015-2047-6"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/bcj.2017.56",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1090307601",
"https://doi.org/10.1038/bcj.2017.56"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/leu.2009.8",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1021356437",
"https://doi.org/10.1038/leu.2009.8"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1186/s13046-014-0111-8",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1015832532",
"https://doi.org/10.1186/s13046-014-0111-8"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/sj.onc.1210028",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1008625838",
"https://doi.org/10.1038/sj.onc.1210028"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/leu.2015.289",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1040701560",
"https://doi.org/10.1038/leu.2015.289"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1186/s13059-014-0550-8",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1015222646",
"https://doi.org/10.1186/s13059-014-0550-8"
],
"type": "CreativeWork"
}
],
"datePublished": "2018-05-15",
"datePublishedReg": "2018-05-15",
"description": "PurposeWe previously showed that carfilzomib (CFZ) has potent anti-proliferative and cytotoxic activity in a broad range of lung cancer cell lines. Here we investigate possible mechanisms of CFZ acquired resistance in lung cancer cell lines.MethodsCFZ-resistant non-small cell lung cancer (NSCLC) cell lines were developed by exposing A549 and H520 cells to stepwise increasing concentrations of CFZ. Resistance to CFZ and cross-resistance to bortezomib and other chemotherapy drugs was measured using the MTT assay. Cytotoxicity to CFZ was determined using a CytoTox assay. Western blot was used to measure apoptosis, autophagy, and drug efflux transporter-related proteins. Quantitative targeted whole transcriptome sequencing and quantitative RT-PCR was used to measure gene expression. Flow cytometry was used to analyze intracellular accumulation of doxorubicin.ResultsThe CFZ IC50 value of the resistant cells increased versus parental lines (2.5-fold for A549, 122-fold for H520). Resistant lines showed reduced expression of apoptosis and autophagy markers and reduced death versus parental lines following CFZ treatment. Both resistant lines exhibited higher P-glycoprotein (Pgp) gene (TempO-Seq\u00ae analysis, increased 1.2-fold in A549, >\u20099000-fold in H520) and protein expression levels versus parental lines. TempO-Seq\u00ae analysis indicated other drug resistance pathways were upregulated. The resistant cell lines demonstrated less accumulation of intracellular doxorubicin, and were cross-resistant to other Pgp client drugs: bortezomib, doxorubicin, and paclitaxel, but not cisplatin.ConclusionsUpregulation of Pgp appears to be an important, but not the only, mechanism of CFZ resistance in NSCLC cell lines.",
"genre": "article",
"id": "sg:pub.10.1007/s00432-018-2662-0",
"inLanguage": "en",
"isAccessibleForFree": true,
"isFundedItemOf": [
{
"id": "sg:grant.2438836",
"type": "MonetaryGrant"
}
],
"isPartOf": [
{
"id": "sg:journal.1313647",
"issn": [
"0171-5216",
"1432-1335"
],
"name": "Journal of Cancer Research and Clinical Oncology",
"publisher": "Springer Nature",
"type": "Periodical"
},
{
"issueNumber": "7",
"type": "PublicationIssue"
},
{
"type": "PublicationVolume",
"volumeNumber": "144"
}
],
"keywords": [
"lung cancer cell lines",
"non-small cell lung cancer cell lines",
"cell lung cancer cell lines",
"cancer cell lines",
"cell lines",
"NSCLC cell lines",
"resistant cell lines",
"protein expression levels",
"CFZ treatment",
"CFZ resistance",
"quantitative RT-PCR",
"drug resistance pathways",
"H520 cells",
"carfilzomib",
"intracellular doxorubicin",
"chemotherapy drugs",
"flow cytometry",
"Western blot",
"autophagy markers",
"resistant cells",
"reduced expression",
"RT-PCR",
"intracellular accumulation",
"MTT assay",
"whole transcriptome sequencing",
"expression levels",
"parental lines",
"doxorubicin",
"cytotoxic activity",
"drugs",
"IC50 values",
"resistance pathways",
"resistant lines",
"possible mechanism",
"apoptosis",
"glycoprotein gene",
"gene expression",
"assays",
"cells",
"TempO-Seq",
"bortezomib",
"less accumulation",
"expression",
"PurposeWe",
"transcriptome sequencing",
"ConclusionsUpregulation",
"paclitaxel",
"cisplatin",
"cytometry",
"death",
"blot",
"treatment",
"Pgp",
"resistance",
"A549",
"markers",
"cytotoxicity",
"accumulation",
"autophagy",
"lines",
"mechanism",
"pathway",
"levels",
"activity",
"protein",
"sequencing",
"genes",
"broad range",
"quantitative",
"concentration",
"analysis",
"values",
"characterization",
"range"
],
"name": "Characterization of carfilzomib-resistant non-small cell lung cancer cell lines",
"pagination": "1317-1327",
"productId": [
{
"name": "dimensions_id",
"type": "PropertyValue",
"value": [
"pub.1103994980"
]
},
{
"name": "doi",
"type": "PropertyValue",
"value": [
"10.1007/s00432-018-2662-0"
]
},
{
"name": "pubmed_id",
"type": "PropertyValue",
"value": [
"29766327"
]
}
],
"sameAs": [
"https://doi.org/10.1007/s00432-018-2662-0",
"https://app.dimensions.ai/details/publication/pub.1103994980"
],
"sdDataset": "articles",
"sdDatePublished": "2022-05-20T07:34",
"sdLicense": "https://scigraph.springernature.com/explorer/license/",
"sdPublisher": {
"name": "Springer Nature - SN SciGraph project",
"type": "Organization"
},
"sdSource": "s3://com-springernature-scigraph/baseset/20220519/entities/gbq_results/article/article_757.jsonl",
"type": "ScholarlyArticle",
"url": "https://doi.org/10.1007/s00432-018-2662-0"
}
]
Download the RDF metadata as: json-ld nt turtle xml License info
JSON-LD is a popular format for linked data which is fully compatible with JSON.
curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s00432-018-2662-0'
N-Triples is a line-based linked data format ideal for batch operations.
curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s00432-018-2662-0'
Turtle is a human-readable linked data format.
curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s00432-018-2662-0'
RDF/XML is a standard XML format for linked data.
curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s00432-018-2662-0'
This table displays all metadata directly associated to this object as RDF triples.
264 TRIPLES
22 PREDICATES
121 URIs
103 LITERALS
18 BLANK NODES